Nachweis von DNA-Doppelstrangbrüchen bei computertomographischen Untersuchungen - Einfluss von Kontrastmittelgabe

Die Computertomographie stellt die Hauptquelle der gegenwärtigen Strahlenexposition der Bevölkerung dar. Nach Bestrahlung sind Doppelstrangbrüche (DSBs) die gravierendsten Läsionen der DNA, da hierbei die genetische Information auf beiden DNA-Strängen unterbrochen wird. Werden Doppelstrangbrüche nic...

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Bibliographic Details
Main Author: Pathe, Caroline
Contributors: Heverhagen, Johannes (Prof. Dr. Dr.) (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2011
Medizin
Subjects:
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Table of Contents: Computed tomography is the main source of present radiation exposure of the population. After radiation, double-strand breaks (DSBs) are the most significant lesion of the DNA because the genetic information is compromised on both DNA-strands. If un- or misrepaired, mutations and malignant degeneration of cells may result. The first part of this work aimed to investigate the induction and repair of double-strand breaks after computed tomography in vivo. To enhance medical imaging, contrast media is frequently applied during the CT scans. The effect these have on the induction and repair of double-strand breaks in vivo is evaluated in the second part of this study. For several years, γH2AX has been used as a marker for detecting DSBs. Since this is the only method that has proven to be sensitive in radiation doses as low as a few mGy, it has become the gold standard for the detection of DSBs in computed tomography´s low dose range. Using a fluorescent antibody specific for γH2AX, double-strand breaks can be visualized as foci. Each focus represents precisely one double-strand break. The loss of γ-H2AX foci in the nucleus reflects the repair of the DNA-double-strand breaks. Blood samples were taken from 47 patients with an average age of 56.8 ± 17.38 years (mean ± standard deviation). All of them underwent a clinically indicated computed tomography at defined points of time (prior as well as 5 min, 1 hr, 2 hrs and 24 hrs af-ter the CT-scan). Lymphocytes were isolated from the blood and the number of foci was quantified by using the γ-H2AX method. In comparison to the background focus level, which was determined by evaluating the blood sample prior to the CT-scan and which reflects the permanent damage of the DNA before the x-ray exposure, the number of foci 5 min after the CT-scan increased by a factor of 4.2. This confirms that CT examinations induce DNA-damage in the form of double-strand breaks and that these can be successfully detected in vivo with the γ-H2AX method. The detected number of foci is consistent with the results of similar studies. The subsequent time points showed a linear decrease of the focus level, reflecting the repair of the induced double-strand breaks. After 24 hrs a residual focus level of 25% remains, which implies that not all of the induced DSBs were repaired. In order to measure the effect of contrast medium on the formation and repair of double-strand breaks, two patient groups were formed. Group I consisted of 21 patients who solely underwent unenhanced CT and were an average age of 59 ± 18.88 years (mean ± standard deviation). Group II was comprised of 26 patients who solely received contrast-enhanced CT and were an average age of 55,04 ± 15,84 years (mean ± standard deviation). 5 min post CT, the contrast-enhanced group II showed an in-crease of 29% in foci levels compared to the unenhanced group I. Since this result suggests that the administration of contrast medium induces additional DNA damage, this should be taken into consideration when estimating the radiation exposure of computed tomography. The greater DNA damage is most likely an effect of an enhanced photoelectric effect due to the high atomic number Z of the iodine in the contrast agent. Thus more secondary radical electrons are generated that damage the DNA. After 24 hrs both groups showed similar residual foci levels. The additional double-strand breaks due to the contrast medium seem to have been repaired. The great interindividual differences in the number of foci between the patients as well as the incomplete repair of the double-strand breaks after 24 hrs have to be emphasized. The cause of the high variance of the DSB numbers and the repair capacity should be explored further as should the period of time the residual double-strand breaks undergo repair, if at all. This study has the character of a preliminary study. In order to draw definite conclusions as to the effect of contrast medium, a follow-up study with a higher number of patients should be initiated. It should take measures to include groups of patients with consistent age structures, sex, pre-existing illnesses, type of CT with similar DLP values and amount of applied contrast medium. And since it is not yet known how the given parameters influence the results, this too could be further investigated.